Investigators from the Family Stress Program and the Development and Genetics Program at the George Washington University and the Department of Psychiatry at the University of Arizona propose a collaborative project to study the interaction of stress and personal vulnerability as they contribute to risk for depression after job loss. The primary goal of this work is to develop and test an integrated theory of how personal vulnerabilities, including genetic susceptibility, shape depressive response in the face of stress. This study is designed specifically to provide information essential for guiding a new generation of preventive interventions for high-risk individuals facing job loss. The study is guided by four aims. First, statewide lists of recently unemployed individuals will be used to accrue a broad community sample of 432 people who have recently lost their jobs.This sample, balanced by gender and including a substantial proportion of African Americans, will then participate in in-home interviews to collect information on depressive symptoms and depressive episodes; a range of personal, financial, and interpersonal stressors associated with job loss; and phenotypic diatheses including prior history of depression, neuroticism, negative attribution style, and attachment style. We will also collect saliva samples from all participants for DNA extraction, in order to study the effects of genetic diatheses involving a functional polymorphism (SLC6A4) of the serotonin transporter (5-HTTLPR) gene on stress-induced depression. Another more exploratory series of genetic markers will also be genotyped to provide more preliminary tests of whether they interact with stress to increase risk for depression. Second, participants will be followed for 30 weeks after the date of job loss, to study the dynamic interplay of stress and vulnerability as they influence depression. Because risk processes may differ over the course of depressive response, we plan to conduct a total of five assessments in order to capture dynamic fluctuations in symptoms over this period that reflect onset, maintenance, and resolution of depression. Third, multilevel modelling will be used to test a general model of how exposure to economic and interpersonal stressors in the months following job loss precipitates, maintains, or exacerbates depressive response, and how these effects are influenced by personal vulnerabilities. This model hypothesizes both sensitization and recruitment effects, such that personal vulnerabilities are predicted to both increase rates of stressors (recruitment) and to moderate the effects of stressors (sensitization) on trajectories of depressive symptoms over the 30-week period. Fourth repeated followup data will be used to test hypotheses concerning the specific mechanisms responsible for these effects. We will test two more proximal models concerning how coping efficacy and social support and undermining mediate the interaction of personal vulnerabilities and stress on depression.